scholarly journals Mesenchymal Stem Cells: A New Choice for Nonsurgical Treatment of OA? Results from a Bayesian Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ziqin Cao ◽  
Yajia Li ◽  
Fuqiang Gao ◽  
Ren Wu ◽  
Pengcheng Dou ◽  
...  

Objective. Osteoarthritis (OA) is the most common degenerative joint disease, causing joint pain, stiffness, and even disability. Guidelines recommend intra-articular injections as an alternative treatment to relieve OA symptoms for patients who demonstrate poor tolerability or compliance to oral administration of drugs. Mesenchymal stem cells (MSCs) are a potential treatment for of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety between hyaluronic acid (HA), corticosteroids (GCs), platelet-rich plasma (PRP), and MSCs. Design. Systematic review and Bayesian network meta-analysis. Data Sources. Relevant studies, published from January 2000 to January 2020, in the PubMed, Cochrane library, EMBASE, and CKNI databases. Methods. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement, improvement in joint stiffness, and risk of adverse effects (AEs) were assessed. Results. Twenty-five articles with 4642 patients were included. Overall, MSC therapy was the most effective treatment for pain relief (standardized mean difference compared with placebo = 3.61 , 95% CI [1.87 to 5.35]). Both MSC and PRP therapies improved every symptom of OA effectively and have an advantage over HA and GCs which are recommended by guidelines. MSCs, PRP, HA, and GCs are tolerated well for patients in long-term treatment of OA compared with placebo. Conclusions. The results show that MSCs relieve pain, stiffness, and dysfunction due to OA better than PRP, HA, and GCs and are not statistically correlated with greater safety concerns. More high-quality trials are needed to reconfirm the findings of this study, however, standardization of preparation of MSCs and PRP should be investigated in the future.

2020 ◽  
Vol 28 (1) ◽  
pp. 230949901988766 ◽  
Author(s):  
Qipeng Wu ◽  
Xuefen Luo ◽  
Yuan Xiong ◽  
Guohui Liu ◽  
Junwen Wang ◽  
...  

Osteoarthritis (OA) is an extremely common form of chronic joint disease which can affect the knees and other joints of older adults, leading to debilitating disability in the knee and consequent reduction in quality of life. Intra-articular platelet-rich plasma (PRP) or hyaluronic acid (HA) injections are effective for maintaining long-term beneficial effects without increasing the risk of intra-articular infection. However, few studies have compared the relative value of HA and PRP for OA treatment. PRP is more effective than HA for OA treatment in recent studies of this topic. We systematically searched Medline, SpringerLink, Embase, Pubmed, Clinical Trials.gov, the Cochrane Library, and OVID for all articles published through May 2018. Any study was included that compared the effect of HA and PRP (consistent treatment cycle and frequency of injection) on patient’s pain levels and functionality improvements. Review Manager 5.3 was used to analyze data regarding these two primary outcomes. We included 10 total studies in the present meta-analysis. International Knee Documentation Committee (IKDC; MD: 10.37, 95% confidence interval (CI): 9.13 to 11.62, p < 0.00001), Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC; MD: −20.69, 95% CI: −24.50 to −16.89, p < 0.00001, I2 = 94%), and Visual Analogue Scale (VAS; MD: −1.50, 95% CI: −1.61 to −1.38, p < 0.00001, I2 = 90%) differed significantly between the PRP and HA groups. Knee Osteoarthritis Outcome Scores (KOOSs) did not differ significantly ( χ2 = 23.53, I2 = 41%, p = 0.11). Our hypothesis appears not to be confirmed because PRP and HA did not differ significantly with respect to KOOS score. However, the IKDC, WOMAC, and VAS scores differed significantly. Thus, based on the current evidence, PRP appears to be better than HA at achieving pain relief and self-reported functional improvement. Ia, meta-analyses of randomized clinical trials.


2021 ◽  
Vol 45 (4) ◽  
pp. 274-283
Author(s):  
Woo Sup Cho ◽  
Sun Gun Chung ◽  
Won Kim ◽  
Chris H. Jo ◽  
Shi-Uk Lee ◽  
...  

Objective To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies.Methods We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose.Results Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed.Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e035346
Author(s):  
Yuchen He ◽  
Hongyi He ◽  
Dong-Xing Xie ◽  
Xiaoxiao Li ◽  
Yilun Wang

IntroductionMost of the patients who received arthroscopic knee surgery will suffer moderate to severe pain, which can delay the rehabilitation process and increase the risk of postoperative complications. Therefore, seeking a safe and effective postoperative analgesia is necessary for promoting the application of arthroscopic surgery. This protocol aims to detail a planned systematic review and meta-analysis on the comparative efficacy and safety of single-dose intra-articular injection of analgesics for pain relief after knee arthroscopy.Method and analysisPubMed, Embase, Web of Science and Cochrane Library will be searched from inception to 1 June 2020 to retrieve randomised controlled trials (RCTs) that compared the commonly used single-dose intra-articular analgesics (ie, morphine; bupivacaine (including levobupivacaine); ropivacaine and magnesium alone or in combination) with placebo or between each other for postoperative pain relief among patients who had received knee arthroscopy. The primary outcome is pain intensity at 2-hour and 24-hour postoperatively; the secondary outcomes include side effects (eg, knee effusion, nausea, vomiting and flushing), the number of patients requiring supplementary analgesia and the time to first analgesic request. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The Bayesian network meta-analysis will be conducted using WinBUGS V.1.4.3.Ethics and disseminationSince no private or confidential patient data will be contained in the reporting, approval from an ethics committee is not required. Our study raises no ethical issue, and the results will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019130876.


2020 ◽  
Vol 9 (10) ◽  
pp. 719-728
Author(s):  
Jiaqian Wang ◽  
Liang Zhou ◽  
Yong Zhang ◽  
Lixin Huang ◽  
Qin Shi

Aims The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728.


2022 ◽  
pp. 036354652110538
Author(s):  
Kang-Il Kim ◽  
Myung-Seo Kim ◽  
Jun-Ho Kim

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited. Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA. Study Design: Meta-analysis; Level of evidence, 1. Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS). Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months ( Z = 7.62; P < .0001) and 12 months ( Z = 7.21; P < .0001) and functional improvement at 6 months ( Z = 4.13; P < .0001) and 12 months ( Z = 3.79; P = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75). Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.


2021 ◽  
Author(s):  
Junwu Wang ◽  
Pengzhi Shi ◽  
Dong Chen ◽  
Shuguang Wang ◽  
Pingchuan Wang ◽  
...  

Mesenchymal stem cells (MSCs) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for the relevant studies published between October 2019 and April 2021 in PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. A total of 22 studies involving 371 patients were included in the present study. MSCs were administered in 247 participants, and MSCs were allogeneic from umbilical cord, adipose tissue, menstrual blood, placenta, Wharton's jelly, or unreported sources. Combined results found that MSCs group significantly reduced the incidence of adverse events (OR = 0.43, 95%CI. = 0.22~0.84, P = 0.01) and mortality (OR = 0.17, 95%CI. = 0.06~0.49, P < 0.01), and the difference compared with control group was statistically significant. No MSCs treat-related serious adverse events were reported. The lung function and radiographic outcomes, and biomarker levels of inflammation and immunity all showed improvement trends. Therefore, MSCs therapy is an effective and safe method in the treatment of COVID-19-associated pneumonia and shows advantages in less adverse events and mortality. However, a standard and effective MSCs treatment program needs to be developed.


Author(s):  
Apurba Barman ◽  
Archana Mishra ◽  
Rituparna Maiti ◽  
Jagannatha Sahoo ◽  
Kaustav Basu Thakur ◽  
...  

Background: To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases.Methods: The PubMed, Medline, and Central databases and trial registries were searched from their inception to July 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). Results: A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8–12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01–14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provide better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6–7 months. Conclusions: PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.


2021 ◽  
Vol 10 (10) ◽  
pp. 650-658
Author(s):  
Anita Sanghani-Kerai ◽  
Cameron Black ◽  
Shuliang Oliver Cheng ◽  
Laura Collins ◽  
Nadine Schneider ◽  
...  

Aims This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658.


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